Hemorrhages and perforations of the mucosal lining of the gastro-intestinal tract are serious medical concerns. Such disorders are often associated with stress and with the ingestion of certain drugs, particularly nonsteroidal anti-inflammatory drugs (NSAIDs) and/or ethanol. New and improved methods for treating disorders such as gastric ulcers, duodenal ulcers, peptic ulcer disease, and non-ulcer dyspepsia are needed. In particular, new methods are needed for a safe and effective gastroprotective therapy for chronic users of NSAIDs. NSAIDs which can cause damage to the mucosal lining of the gastrointestinal tract include, but are not limited to aspirin and other salicylates, ibuprofen, ketoprofen, naproxen, ketorolac, flurbiprofen, piroxicam, meclofenamate sodium, phenylbutazone, sulindac, difunisal, indomethacin, etodolac, fenoprofen calcium, mefenamic acid, tolmetin sodium and diclofenac sodium.
The following references disclose certain compounds related to flavone having various effects on the gastrointestinal system; some are disclosed to have anti-ulcer activity: Belgian Patent No. 888,982 of Fabrica Espanola de Productos Quimicos y Farmaceutics, S. A., published Sep. 16, 1981; Japanese Patent No. 70-24111 of Taisho Pharmaceutical Co., Ltd., published Nov. 10, 1972; Japanese Patent No. 72-32888 of Taisho Pharmaceutical Co., Ltd., published Dec. 15, 1973; Japanese Patent No. 72-032889 of Taisho Pharm. Co., published Dec. 15, 1973; Japanese Patent No. 74-093023 of Taisho Pharmaceutical KK, published Feb. 24, 1976; Japanese Patent Application No. 78-098452 of Taisho Pharmaceutical KK, published Feb. 27, 1980; French Patent No. 011,196 of Fabrica Espanola de Productos Quimicos y Farmaceutics, S. A., published Nov. 10, 1980; Swiss Patent No. 126,197 of Khark Chem. Pharm., published May 13, 1977; German Patent No. 615,710 of Hoechst AG, published Nov. 11, 1987; Obolentseva, G. 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Abu-Jayyab, "The Gastric Anti-Ulcer Activity of Khat (Catha edulis Forsk): Investigations on its Flavonoid Fraction", Research Communications in Substances of Abuse, Vol. 5, No. 2 (1984), pp. 157-160; Villar, A., M. A. Gasco & M. J. Alcaraz, "Antiinflammatory and Anti-ulcer Properties of Hypolaetin-8-glucoside, a Novel Plant Flavonoid", J. Pharm. Pharmacol., Vol. 36 (1984), pp. 820-823; Barnaulov, O. D., O. A. Manicheva & N. F. Komissarenko, "Comparative Evaluation of the Effect of Some Flavonoids on Changes in the Gastric Wall of Reserpine-Treated or Immobilized Mice", Khim.-Farm. Zh., Vol. 17, No. 8 (1983), pp. 946-951; Barnaulov, O. D., O. A. Manicheva, V. L. Shelyuto, M. M. Konopleva & V. I. Glyzin, "Effect of Flavonoids on the Development of Experimental Dystrophy of the Stomach in Mice", Khim.-Farm. Zh., Vol. 18, No. 8 (1984), pp. 935-941; Barnaulov, O. D., O. A. Manicheva, I. I. Chemesova & N. F. Komissarenko, "Comparative Evaluation of the Effect of Flavonoids on the Development of Experimental Lesions in the Mouse Stomach", Khim.-Farm. Zh., Vol. 18, No. 11 (1984), pp. 1330-1333; Barnaulov, O. D., O. A. Manicheva, R. K. Yasinov & G. P. Yakovlev, "Evaluation of the Effect of Flavonoids from the Aerial Parts of Astragalus Quisqualis Bunge and A. Floccosifolius Sumn. on the Development of Experimental Lesions in the Mouse Stomach", Rastit. Resur., Vol. 21, No. 1 (1985), pp. 85-90; Konturek, S. J., M. E. Kitler, T. Brzozowski & T. Radecki, "Gastric Protection by Meciadanol--A New Synthetic Flavonoid-Inhibiting Histidine Decarboxylase", Digestive Diseases and Sciences, Vol. 31, No. 8 (Aug. 1986), pp. 847-852; Goel, R. K., V. B. Pandey, S. P. D. Dwivedi & Y. V. Rao, "Antiinflammatory and Antiulcer Effects of Kaempferol, a Flavone, Isolated from Rhamnus procumbens", Indian Journal of Experimental Biology, Vol. 26 (February 1988), pp. 121-124; Rainova, L., N. Nakov, S. Bogdanova, E. 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It is an object of the subject invention to provide methods of using certain substituted flavone compounds as gastroprotective agents.
It is a further object of the subject invention to use such compounds particularly for protection against NSAID-induced damage to the gastric lining.
It is also an object of the subject invention to provide compositions comprising certain substituted flavone compounds for use as gastroprotectants.